A growing body of evidence indicates that IgA1 present in the serum of patients with IgA nephropathy (IgAN) displays aberrant structural properties in its carbohydrate side chains. Increased serum levels of IgA1 may be related to the recently shown deficient galactosyation of IgAN IgA1 demonstrated by lectin-binding studies and direct analyses of igA1 isolated from sera of IgAN patients. This galactose (Gal) deficiency appears to be restricted to the hinge region of glycans of IgA1, which are primarily responsible for interactions with the asialoglycoprotein receptor (ASGP-R) and catabolism of IgA1 by hepatocytes. The absence of Gal exposes the new terminal sugar. N-acetylgalactosamine (GalNAc) as demonstrated by an increased reactivity of serum IgA1 from patients with IgAN GalNAc-specific lectins. The possible relationship between the aberrant glycosylation of IgA1 and IgAN was indicated by an observation which demonstrated the presence of a receptor on human mesangial cells that binds but does not internalize degalactosylated IgA1. In this project, we propose to test the following hypothesis: Gal-deficiency of a small population of IgA1 molecules (due to the functional deficeincy of beta 1-3 galactosyltransferase [Beta 1-3GT] in IgA1-producing cells of patients with IgAN), leads to alterations in their elimination from the circulation and their liver catabolism, and results in their deposition in kidney mesangia. The overall goal is to determine if the aberrant glycosylation of IgA1 is the underlying cause of IgAN. In addition to providing potential diagnostic procedures for the early identification of children at risk for the development of IgAN, these studies may suggest a rational basis for the design of effective therapeutic approaches. This project will obtain serum samples from 50 healthy adults to use as control samples in studies of the molecular abnormalities of immuno- globulin A in IgA nephropathy. Prospective subjects are screened by a brief physical examination and questionnaire before a 20-ml venous blood sample is drawn.